Biomedical subjects
Publications and source records attributed to H C Lou.
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The neural mechanisms involved in learning disorders are largely unknown. We studied three-dimensional regional cerebral blood flow (rCBF) in 13 children with dysphasia and/or attention deficit disorder (ADD), using xenon 133 inhalation and emission computed tomography. The rCBF distribution was abnormal in both hemispheres in all patients, as compared with the mean CBF distribution of nine normal children. Regions of hypoperfusion and, by inference, low metabolic activity were predominantly seen in the periventricular white matter and in border zones between major arterial territories. In patients with dysphasia, parts of both perisylvian regions were hypoperfused, and object-naming tasks failed to produce an increased flow in relevant cortical regions. Patients with different dysphasic syndromes appeared to have different patterns of rCBF. All 11 patients with ADD had hypoperfusion in the white matter of the frontal lobes and seven also in the caudate nuclei region. Methylphenidate hydrochloride increased perfusion in the central region, including the mesencephalon and the basal ganglia, and decreased perfusion of motor and primary sensory cortical areas. The location of hypoperfused structures in cognitive disorders of childhood is consistent with a role for an early hypoxic-ischemic event in their origin.
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During a survey of neuronal ceroid lipofuscinosis (Batten's disease), two younger siblings of patients were found to have the characteristic vacuolation in 11 to 17 per cent of their lymphocytes. The children were four to five years of age and did not have any overt signs or symptoms of the disease. However, they both had markedly reduced auditory memory-span before decreased vision and funduscopic changes developed. The subsequent course of the disease confirmed the diagnosis. It is concluded that neuronal ceroid lipofuscinosis may affect mental functions much earlier than previously believed.
In infants who die during the first months of life necrotic foci are almost invariably found. They are, as a rule, located in border zones between vascular territories, suggesting cerebral ischemia as a pathogenetic mechanism. Normally, the brain is protected against changes in perfusion pressure by autoregulation of cerebral perfusion. In utero, this mechanism is extremely fragile, and normal birth is a sufficient hypoxic insult to abolish autoregulation. Abolished autoregulation has been demonstrated in distressed newborns: Even mild hypotension, which is a common occurrence in these infants during the first few hours of life, is sufficient to induce ischemia. Follow-up studies at the ages of one and four years have shown neonatal ischemia to be the decisive factor in the development of atrophic encephalopathy and motor and cognitive dysfunction. This clarification of the pathogenetic process has important implications for prevention, which is briefly discussed.
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Mean arterial blood pressure (MABP) was measured continuously for 3 to 5 days after birth in 27 premature infants with a birth weight under 1500 g, and who required umbilical artery catheterisation. All had respiratory distress syndrome (RDS). Intraventricular hemorrhage (IVH) occurred in 9 infants (33%), diagnosed by computered tomography (CT). IVH was more common in infants of lower gestational age, in infants delivered vaginally and in infants with perinatal asphyxia. Variable increases in MABP over the resting value occurred in all infants associated with increases in both active and passive motor activity. In 6 infant pairs matched for birth weight, gestational age, mode of delivery and severity of perinatal asphyxia, the infants who developed IVH had higher peak MABP valued compared to matched controls. Resting and minimum MABP values were not different in the two groups. We conclude that the large increases in arterial blood pressure which occur with both spontaneous motor activity and in association with nursing procedures, are an important cause of development of IVH in very low birth weight infants. An example is given to show that pressure peaks can be abolished by phenobarbitone sedation.
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Perinatal hypoxic-ischemic brain damage and intraventricular hemorrhage (IVH) are important causes of death and neurologic and intellectual dysfunction. Both lesions are related to perinatal asphyxia, and the aim of our review is to establish a comprehensive pathogenetic model. Our previous finding that cerebral blood flow is pressure-passive in perinatal distress is crucial, as periods of hypertension and hypotension alternate in the distressed infant. In hypertension, transmural pressure increases in the capillaries, leading to edema and, in premature infants, eventual rupture of vessels and IVH. Intraventricular hemorrhage induces vasospasm and ischemia. Ischemia is the direct result of hypotension. Cerebral blood flow studies performed a few hours after birth with subsequent examinations at one year of age point to a decisive effect of neonatal ischemia on subsequent development.
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Computerised tomography has revealed that more than 40% of premature neonates (birth weight smaller than 1500 g) have cerebral bleeds in the first 3 or 4 days of extrauterine life. Injection studies done at necropsy have shown that they usually originate in the capillaries of the germinal matrix. It is suggested that premature neonates are hypertensive when their blood-pressure is compared with that in utero, and that events that lead to further rises in pressure are common. Their capillaries are not protected against rises in arterial pressure because autoregulation is impaired. Furthermore, the capillaries in the germinal matrix are not supported by firm glial structures. Arterial pressure rises are therefore likely to be responsible for germinal matrix haemorrhage in the premature neonate, and the risk of haemorrhage probably diminishes as autoregulation of cerebral blood-flow is restored a few days after birth.
Cerebral blood flow was measured, using the 133Xe clearance technique, a few hours after birth in 19 infants with varying degrees of respiratory distress syndrome. Ten of these infants had had asphyxia at birth. The least affected infants with normotension (systolic blood pressure 60 to 65 mm Hg) had CBF values of about 40 ml/100 gm/minute. Hypotensive infants with asphyxia at birth or RDS or both had values for CBF of about 20 ml/100 gm/minute, or less. CBF was strongly correlated with the arterial blood pressure, showing a linear relationship that was identical in infants with asphyxia at birth and infants with RDS only. CBF varied considerably with spontaneous variations in blood pressure, suggesting that autoregulation was lacking. This finding may explain why distressed premature infants are prone to develop massive capillary bleeding in the germinal layer with penetration to the ventricles.
Among 19 infants in whom cerebral blood flow had been determined a few hours after birth, four died during the first days or weeks after birth, all with massive intracranial hemorrhage. The other infants were examined at 9 to 12 1/2 months of age by means of clinical neurologic evaluation, developmental psychologic assessment (Cattell), EEG, and cranial computed tomography. Six of the ten infants who had had CBF of 20 ml/100 gm/minute or less had developed cerebral atrophy as demonstrated at autopsy or by CT scan, none with neonatal flows above 20 had done so. Only one in the low flow group had developed completely normally, whereas abnormal development was found in only a minority of the high flow group. No other neonatal observation had such a clear relationship to later development. It is concluded that CBF of 20 or less during the first hours of life is critical.
Cerebral blood flow (CBF) was studied in non-exteriorized near-term sheep fetuses using the radioactive microsphere technique. By partially occluding the umbilical vessels for a period of 1--1 1/2 hours a progressive and severe asphyxia with a final arterial pH of 6.90 was achieved. Varying the mean arterial blood pressure in the fetuses by blood withdrawal or infusion in this state, CBF was measured at different perfusion pressures (mean arterial blood pressure (MABP) minus central venous pressure (CVP)). A passive flow/pressure relationship--loss of autoregulation--was found, with hyperemia reaching CBF values up to 6 times normal at normal MABP of about 60 to 70 mmHg, and severe ischemia reaching CBF values close to zero in large cortical areas at MABP of 30 mmHg. CVP remained essentially unchanged at 10--15 mmHg. The severe and prolonged asphyxia rendered the blood-brain barrier leaky to the albumin tracer Evans blue. In four other fetuses umbilical cord clamping was omitted. However, only in one of these cases was acidosis completely avoided, and CBF autoregulation maintained. The three other fetuses were acidotic at the end of the surgical procedure and had impaired autoregulation.
A three-generation transmission of under five percentile values for serum low density lipoprotein and low density lipoprotein cholesterol typical of heterozygous familial hypobetalipoproteinemia was demonstrated in a Danish family. Slight clinical signs of CNS abnormality were found in 4 of the 8 subjects with heterozygous familial hypobetalipoproteinemia, but did not resemble the neurological findings in abetalipoproteinemia nor in the previously described patients with familial hypobetalipoproteinemia. There were no signs of myelin dysfunction in the central nervous system as judged from the normal latency of visual and somatosensory evoked potentials.
In nine distressed newborn infants, mean aortic blood pressure and motor activity were recorded continuously during the first two or three days of life. Six of the infants had been asphyxiated at birth, the remainder having idiopathic respiratory distress only. The results showed that mean arterial blood pressure varies synchronously with motor activity, reaching maximum values much higher than previously suspected: about 90 or 100 mmHg were recorded in several infants. In three cases focal and/or generalized epileptic seizures occurred during the recording. It was found that in these circumstances too blood pressure increases dramatically, even if the motor component of the seizure is insignificant.